Objective: Three research articles published in late 1995 and early 1996 suggested that oral contraceptives containing either of the newer progestogens (gestodene or desogestrel) could be associated with an increased risk of venous thromboembolism. During the months after the initial publications, the results have been scrutinized with great care and further studies have been published. The findings of 2 recent database studies, 1 in the United Kingdom and 1 in Germany, are presented in this article.
Patterns of use: The average age of users of combined oral contraceptives in Germany was 27 years, compared with 26 years in the United Kingdom. In Germany the use of gestodene-based products was lower than that in the United Kingdom. In the United Kingdom the users of desogestrel with 20 microg ethinyl estradiol (Mercilon) were older than the users of desogestrel with 30 microg ethinyl estradiol (Marvelon).
Crude incidence: The crude incidence of venous thromboembolism in the UK study was 4.1 cases/10,000 woman-y exposure to combined oral contraceptives. In Germany it was 4.2 cases/10,000 woman-y. In Germany the rates among users of second-generation combined oral contraceptives were higher than those among users of third-generation products. The reverse was the case in the United Kingdom. In the United Kingdom the crude incidence rates were higher for the 20 microg estrogen desogestrel product than for the 30 microg product. CASE-CONTROL ANALYSIS: The adjusted odds ratios in the UK study did not show significant increases for desogestrel or gestodene compared with levonorgestrel products. There were inconsistencies in the results among centers in the 2 international studies (the World Health Organization and Transnational studies). In both there was a consistent inverse dose-response relationship with estrogen in all centers.
Conclusion: The limitations of the observational studies are such that the hypothesis that the newer progestogens are more likely to cause venous thromboembolism cannot be proved.
PIP: Research articles published in 1995-96 suggested that oral contraceptives (OCs) containing desogestrel or gestodene are associated with an increased risk of venous thromboembolism. This paper presents the findings of two more recent studies on this association, one from the UK and the other from Germany, both of which were based on general practice computer-generated clinical databases. The median age of OC users was 26 years in the UK study and 27 years in the German study. The crude incidence of venous thromboembolism per 10,000 woman-years of OC exposure was 4.1 cases in the UK study and 4.2 cases in Germany. In Germany, this rate was higher among users of second-generation OCs (4.03 cases per 10,000 woman-years) than third-generation OCs (3.95 cases per 10,000 woman-years). In the UK, the reverse pattern was found: 4.96 and 3.10 cases per 10,000 woman-years for third- and second-generation products, respectively. Moreover, crude incidence rates were higher for the 20 mcg estrogen-desogestrel formulation than for the OC containing desogestrel and 30 mcg of estrogen--a biologically implausible finding. The adjusted odds ratios in the UK study did not show any significant increases in venous thromboembolism risk for desogestrel or gestodene compared with levonorgestrel. Overall, these findings fail to provide support for the hypothesis that the newer progestogens are more likely to cause venous thromboembolism.